不同剂量氟尿嘧啶缓释植入剂腹腔给药治疗H22小鼠腹水瘤疗效的实验研究  

Effect of different doses of sustained-release fluorouracil on mice bearing H22 ascitic tumor intraperitoneally

作　　者：梅魁敏[1] 秦叔逵[2] 殷晓进[3] 陈亚利[3] 魏红梅[2] 张改琴[1] 李苏宜[4] 

机构地区：[1]东南大学医学院,南京210009 [2]解放军八一医院全军肿瘤中心,210002 [3]江苏先声药物研究有限公司研究院,210042 [4]东南大学附属中大医院肿瘤科,210009

出　　处：《临床肿瘤学杂志》2011年第5期389-392,共4页Chinese Clinical Oncology

摘　　要：目的探讨不同剂量氟尿嘧啶缓释植入剂(中人氟安)治疗小鼠恶性腹腔积液的有效性和安全性。方法采用肝癌H22细胞株建立小鼠腹水瘤模型,68只成模小鼠随机分为4组,即赋型剂对照组、中人氟安低剂量组(2mg/只)、中剂量组(4mg/只)和高剂量组(6mg/只)。观察小鼠的一般状态、体重变化和生存期,计算腹水体积并计数腹水内肿瘤细胞,流式细胞仪检测腹水肿瘤细胞凋亡及细胞周期。结果与对照组相比,中人氟安三个剂量组小鼠的一般状态良好,体重增长缓慢,全身症状出现较晚,中位生存期均有延长(16、20、20天vs.13天,P<0.01),但中、高剂量组间生存期差异无统计学意义(P>0.05)。实验第13天,中人氟安低、中、高3个剂量组的腹水体积(m l)分别为9.2±0.9、5.6±1.0和5.9±1.1,每毫升中的肿瘤细胞数分别为(10.11±1.31)×108、(7.25±1.00)×108和(7.47±1.11)×108,均少于对照组的(13.3±1.5)m l和(14.73±1.25)×108(P均<0.01);腹水肿瘤细胞的凋亡率分别为(14.8±1.4)%、(23.9±2.6)%和(21.5±3.1)%,S期比例分别为(31.23±3.26)%、(50.17±4.60)%和(47.08±4.11)%,均高于对照组的(7.6±1.9)%和(20.57±4.08)%(P均<0.01),其中中、高剂量组与低剂量组的差异具有统计学意义(P<0.05),而中、高剂量组差异无统计学意义(P>0.05)。结论中人氟安对于实验小鼠H22腹水瘤的形成具有良好的控制作用,可以延长腹水瘤小鼠的生存期,且安全性好,以中剂量组的效果最佳。因此,提示在临床上对于恶性腹腔积液和腹膜转移的患者,可以应用中人氟安进行局部治疗,但需选择合适的剂量。Objective To investigate the effect of sustained-release fluorouracil（Sinofuan） injected intraperitoneally on the mice with ascitic tumor.Methods Mouse models bearing ascites tumors were established via injecting H22 cells intraperitoneally.Sixty-eight model mice were assigned into 4 groups randomly,the control group,the low-dose（2mg）,medium-dose（4mg）,high-dose（6mg） Sinofuan group.The mice＇s general states,body weight and survival time were observed.The cumulative ascites volume and number of tumor cells were calculated.The apoptosis rates and cell cycle of tumor cells were analyzed with flow cytometry.Results Compared with the control group,the three Sinofuan groups showed better general state,slower body weight increase and longer medium survival（16.0,20.0,20.0 verse 13.0 days;P0.01）.Ascites accumulation of three Sinofuan groups（low-,medium-,high-dose） were 9.2±0.9ml,5.6±1.0ml and 5.9±1.1ml;the count of ascites tumor cells per milliliter were（10.11±1.31）×108,（7.25±1.00）×108 and（7.47±1.11）×108,all of which were lower than that of control group（13.3±1.5ml and 14.73±1.25×108）,with significant differences（P0.01）.The apoptosis rates were 14.8±1.4%,23.9±2.6% and 21.5±3.1% respectively,and S phase percentages were 31.23±3.26%,50.17±4.60% and 47.08±4.11%,all of which were higher than that of control group（7.6±1.9% and 20.57±4.08%）,showing significant differences（P0.01）.The differences between the medium-and high-dose group were not significant（P0.05）.Conclusion Sinofuan,especially in medium-dose,shows a good effect and safety in the treatment of the mice bearing H22 ascites tumors.It suggests that Sinofuan may be applied to treat the malignant ascites and peritoneal metastases in appropriate doses.

关 键 词：氟尿嘧啶缓释植入剂/中人氟安 腹腔内化疗 H22细胞株 恶性腹腔积液 

分 类 号：R73-36[医药卫生—肿瘤]